Paradigms of growth control: relation to Cdk activation

The cyclin-dependent kinases (CDKs) play a key role in cell cycle control, and in this review, we focus on the events that regulate their activities. Emphasis is placed on the CDKs that function during the G(1) phase of the cell cycle and on the CDK inhibitor p27(Kip1). We discuss how CDK activation relates to two basic concepts of cell cycle regulation: (i) the need for multiple mitogens for the proliferation of nontransformed cells and (ii) the inhibitory effect of high culture density on proliferative capacity. We also describe how Cdk2 modulates the expression of the alpha subunit of the interleukin-2 receptor in T cells, and address the question of whether p27(Kip1) functions as an activator or inhibitor of the CDKs associated with the D cyclins.